Incubation system and method for automated cell culture and testing

Abstract

Incubation system and method for automated cell culture and/or testing. An exemplary incubation system may comprise a housing forming a chamber. A rack may define storage positions to support an array of sample holders inside the chamber. A detection robot may be configured to capture one or more images of cells contained by one or more wells of each sample holder while the sample holder remains at one of the storage positions of the rack. A fluid handling station may be configured to add fluid to, and/or remove fluid from, one or more wells of each of the sample holders inside the housing. At least one plate robot may be configured to move sample holders between the rack and the fluid handling station. A computer may control operation of the detection robot, the fluid handling station, and the at least one plate robot.

We claim: 
     
         1 . A method of automated cell culture and/or testing, the method comprising:
 moving a detection robot along three orthogonal axes to capture one or more images of cells contained in one or more wells of each sample holder of a plurality of sample holders, the plurality of sample holders being stored at storage positions defined by a rack inside an incubator, wherein the sample holder remains in its storage position in the rack as the one or more images are captured for the sample holder;   moving the sample holder from the rack to a fluid handling station inside the incubator using a plate robot; and   removing fluid from, and/or adding fluid to, at least one well of the sample holder at the fluid handling station based on the captured images.   
     
     
         2 . The method of  claim 1 , wherein capturing one or more images is performed lenslessly. 
     
     
         3 . The method of  claim 1 , wherein capturing one or more images includes:
 capturing one or more images for each well of a plurality of wells of the sample holder, and   processing the one or more images to obtain a value corresponding to a confluence and/or density and/or number of cells in the well, and/or morphology, and/or size, and wherein the step of moving is performed for the sample holder if the value(s) for one or more wells of the plurality of wells meets one or more predefined criteria.   
     
     
         4 . The method of  claim 1 , the method further comprising
 sending to a user one or more images of cells resulting from the step of capturing one or more images;   receiving a command from the user to perform the step of moving; and   removing and/or adding fluid at the fluid handling station in response to the command.   
     
     
         5 . The method of  claim 1 , the method further comprising applying local heat via a plurality of local heaters within the incubator to each sample holder before capturing one more images for the sample holder, to reduce condensation on a lid thereof. 
     
     
         6 . The method of  claim 5 , wherein the plurality of local heaters are separated from one another with sufficient clearance for access by the detection robot. 
     
     
         7 . The method of  claim 1 , the method further comprising applying local heat via a dedicated local heater in advance of capturing the one or more images, to allow sufficient time for condensation to be eliminated. 
     
     
         8 . The method of  claim 7 , wherein the application of local heat to a storage position is controlled independent of heaters for other storage positions. 
     
     
         9 . The method of  claim 1 , wherein the user comprises a remote user, and the method further comprises receiving commands from the remote user on whether and/or how to process cultures of the cells depicted in the sent images. 
     
     
         10 . The method of  claim 1 , further comprising using a lid robot to remove a lid of the sample holder to permit fluid addition to and/or removal from, the at least one well, and to replace the lid when fluid transfer is complete. 
     
     
         11 . The method of  claim 1 , wherein capturing one or more images includes illuminating the cells and capturing two or more images representing at least similar fields of view of the illuminated cells but (i) different z-positions of the detection robot that captures the two or more images, (ii) different angles of incidence of illumination, (iii) different wavelengths of illumination, and/or (iv) sub-pixel shifts in lateral position of the detection robot and/or a light source. 
     
     
         12 . The method of  claim 1 , wherein removing and/or adding fluid includes transferring liquid from the at least one well of the sample plate holder to a well of an assay plate. 
     
     
         13 . The method of  claim 12 , further comprising transporting the assay plate from the incubator to an entry/exit chamber of the incubator using a plate robot. 
     
     
         14 . The method of  claim 1 , wherein removing and/or adding fluid includes removing old culture medium from the at least one well, and adding new culture medium to the at least one well, to feed cells in the at least one well. 
     
     
         15 . The method of  claim 1 , wherein the added fluid is moved from stored in vessels outside the incubator to the at least one well.